Since at least 1884, surgeons have sought a means to improve the cosmetic rehabilitation of the anophthalmic patient. Accordingly, improvements have been sought by increasing the support of the artificial eye and by attempts to transfer all latent muscle movement directly to the artificial eye via some form of direct coupling between the eye and the implant. (Ruedemann A. D., "Plastic Eye Implant" Amer J Ophthalmol (1946) 29:947-952).
Ocular implants are used to replace the volume lost after enucleation or evisceration to improve the cosmetic psychological and rehabilitation of the anophthalmic patient. Many materials have been used for this purpose, starting with Mules's hollow glass spheres in 1884. (Mules, P. H., "Evisceration of the Globe, with Artificial Vitreous" Trans Ophthalmol Soc UK (1885) 5:200-206) Mules employed a hollow glass sphere; this sphere offered some support for the upper eyelid but was unable to relieve the chronic downward pressure on the lower lid. (Id.) It is necessary to avoid chronic downward pressure on the lower lid to alleviate the lid sag characteristic of long-term anophthalmic patients. (Ruedemann A. D., "Plastic Eye Implant" Amer J Ophthalmol (1946) 29:947-952, Durham D. G., "The New Ocular Implants" Am J Ophthalmol (1949) 32:79-89).
Numerous implant innovations followed Mules' implant, including implants composed of: gold, cartilage, fat, fascia lata, bone, xenogeneic animal eyes, silver, Vitallium, platinum, aluminum, sponge, wool, rubber, silk, catgut, peat, agar, asbestos, cork, ivory, paraffin, Vaseline, celluloid, and silicone. For example, silicone implants have included spheres of various designs, including those which are solid, hollow, and inflatable. Glass beads have also been used to fill irregular cavities in the orbit (Gougelmann, H. P., "The Evolution of the Ocular Motility Implant" Int Ophthalmol Clin (1976) 10:689-711). Most of the implants composed of these materials were fully buried in the orbit, which was the usual procedure prior to 1941. (Gougelmann, H. P., "The Evolution of the Ocular Motility Implant" Int Ophthalmol Clin (1976) 10:689-711).
In 1941, a combined implant and acrylic prosthesis was introduced by Ruedemann (Ruedemann, A. D., "Plastic Eye Implant" Amer J Ophthalmol (1946) 29:947-952). The extraocular muscles were attached to the posterior portion of this implant, which was covered with gauze. This Ruedemann implant was eventually abandoned, since it had to be manufactured before each operation, and further because secondary strabismus procedures were often required to correct late position problems. This implant was partially exposed and partially buried.
There have been many other design variations of orbital implants since the Ruedemann eye, including several implants that when placed were partially exposed and partially buried, these implants allowed "interaction" with an externally placed, contact lens-type artificial eye through some exposed means, such as pegs, pins, or screws (Gougelmann, H. P., "The Evolution of the Ocular Motility Implant" Int Ophthalmol Clin (1976) 10:689-711).
These partially exposed implants imparted good motility to the artificial eye, but were prone to infection and extrusion. Buried implants were then developed to provide motility through special contours on the anterior aspect of the implant which matched corresponding contours on the posterior aspect of the eye. Other buried implants employed magnets to achieve a form of coupling between the implant and the eye.
Cutler employed a prosthesis comprising an implant with a peg to completely support the weight of the artificial eye and transfer all latent movement to the eye; however, these Cutler prostheses resulted in high rates of infection due to the inability of the material from which the implant was formed to support robust wound closure at the peg-implant interface. (Cutler M. L., "A Positive Contact Ball and Ring Implant for Use after Enucleation" Arch Ophthal (1947) 37:73-81).
In recent years, porous ocular implants composed of hydroxyapatite (HA) and porous polyethylene (PP) have become accepted alternatives to traditional, nonporous spheres composed of silicone or acrylic.
There is some variation in the art concerning the term "integration". The term is used to denote any connection between tissues of the recipient and the implant (e.g. suturing an extraocular muscle to a wire loop). However, as used in the context of the present invention, integrated implants are porous implants capable of sustaining fibrovascular in growth. Porous implants have the advantage of becoming infiltrated by fibrovascular tissue, thereby providing resistance to infection, migration, and extrusion. (Merritt, K., et al., "Implant Site Infection Rates with Porous and Dense Materials" J Biomed Mater Res (1979) 13:101-8; Rosen, H. M., "The Response of Porous Hydroxyapatite to Contiguous Tissue Infection" Plast Recontr Surg (1991) 88:1076-80; Dutton, J. J., "Coralline Hydroxyapatite as an Ocular Implant" Ophthalmology (1991) 98:370-7; Shields, C. L, et al., "Lack of Complications of the Hydroxyapatite Orbital Implant in 250 Consecutive Cases" Trans Am Ophthalmol Soc (1993) 91:177-189; discussion 189-95).
An integrated implant also offers the possibility of good motility for an artificial eye by use of a motility/support peg. Furthermore, an integrated implant that incorporates a motility/support peg may (by supporting the artificial eye) also help prevent the development of a deep superior sulcus and entropion or ectropion of the lower lid, and may reduce other long-term structural defects due to chronic weight and pressure from the artificial eye. (Gougelmann, H. P., "The Evolution of the Ocular Motility Implant" Int Ophthalmol Clin (1976) 10:689-711).
Not all porous implants can transfer implant movement directly to the artificial eye via a motility/support peg. Porous HA implants have the ability to accept a motility/support peg because, when fully vascularized, they can support complete epithelialization of the internal surfaces of the peg hole, thereby sealing the implant from the external environment and preventing infection. Porous polyethylene has only recently been coupled to the eye in this manner. Generally, porous polyethylene implants impart some motility through movement of the fornices, when the extraocular muscles are surgically connected to the fornices or to the implant.
Vascularization can be a lengthy process in porous implants, requiring 6 to 10 months or longer in some cases (Dutton, J. J., "Coralline Hydroxyapatite as an Ocular Implant" Ophthalmology (1991) 98:370-7). Peg placement is usually delayed until the implant shows a high degree of fibrovascular ingrowth, as established by some objective means, such as a bone scan or MRI. (Baumgarten, D., et al., "Evaluation of Biomatrix Hydroxyapatite Ocular Implants with Technetium-99m-mdp" J Nucl Med (1993) 34:467-468; DePotter, P., et al., "Role of Magnetic Resonance Imaging in the Evaluation of the Hydroxyapatite Orbital Implant" Ophthalmology (1992) 99:824-830) Since drilling of the implant for placement of the motility/support peg is usually delayed until the implant is fully vascularized, the complete rehabilitation of the patient can be limited by the speed and degree of fibrovascular ingrowth. Therefore, rapid, complete vascularization of these implants is desirable. Previous efforts to speed the process have included drilling holes in HA implants (Ferrone, P. J., and Dutton, J. J., "Rate of Vascularization of Coralline Hydroxyapatite Ocular Implants" Ophthalmology. (1992) 99:376-379) and cutting windows in any coating materials, such as donor sclera, used to wrap the implant, in order to increase direct contact between the HA material and the highly vascular tissues of the orbit.
In particular, porous HA implants have the known ability to accept a motility/support peg, making possible the direct transfer of implant movement to the artificial eye. Preferred support pegs include those such as disclosed in copending application Ser. No. 08/241,960, filed May 12, 1994; Ser. No. 08/853,647 filed May 9, 1997; and, Ser. No. 08/886,600 filed Jul. 1, 1997, each in the name of Arthur C. Perry, and each of which are fully incorporated by reference herein.
Since the cosmetic and psychological rehabilitation of the anophthalmic patient may depend on life-like movement and position of an artificial eye, compositions and methods are needed to increase the speed of fibrovascular ingrowth into an implant, since such ingrowth is a precondition of drilling the implant to accept the motility/support peg.
Popular coralline HA implants currently available have a reported pore size of 500 .mu.m (HA500) (Interpore 500, Interpore International, Irvine, Calif.); these implants provide excellent fibrovascular ingrowth, but have a rough outer surface that may lead to exposure of the implant following surgery, due to abrasion of the overlying conjunctiva and Tenon's capsule. To avoid implant exposure, current practice calls for coating the implant in some material, such as donor sclera or fascia lata. (Perry, A. C., "Integrated Orbital Implants" Adv Ophthalmic Plast Reconstr Surg (1990) 8:75-81). However, concerns about HIV infection and the additional surgeries needed to harvest a donor coating material have led to a search for suitable alternative coatings. (Dutton, J. J., "Coralline Hydroxyapatite as an Ocular Implant" Ophthalmology (1991) 98:370-7). Accordingly, there is a need for an ocular implant material having a smoother implant surface. A smoother implant surface could reduce abrasion on the orbital tissues during and after implantation, facilitates deeper placement of the implant in the orbit, and can reduce intraoperative time because the implant may not need to be surrounded by an additional coating.
It has been found that both hydroxyapatite and porous polyethylene implants are capable of complete vascularization. The hydroxyapatite implants vascularize more rapidly than the commercially available porous polyethylene (MedPor, Porex Surgical, College Park, Ga.). When the interstitial pore size of the PP was increased to a reported pore size of approximately 400 microns, which corresponded to the reported pore size of commercially available HA (e.g., Interpore, Irvine, Calif.), the rate and extent of vascularization of PP and HA were more similar, a is finding that indicated that increasing the interstitial pore size favorably influenced vascularization of porous implants. (Rubin, P. A. D., et al. "Comparison of Fibrovascular Ingrowth Into Hydroxyapatite and Porous Polyethylene Orbital Implants" Ophthalmic Plastic and Reconstructive Surgery 10(2):96-103 (1994)).
Thus, it was found that PP with pore sizes in the 400 micron range, resulted in more optimal orbital tissue ingrowth than a denser PP implant having an interstitial pore size of approximately 150 microns. It was noted by the authors of the previous study that it was not clear to what extent a further increases in pore size would enhance vascularization, providing guidance in the art that even larger pore sizes were desirable. Again, it was noted that there was a need for maximizing the rate and extent of fibrovascular ingrowth, while minimizing the inflammation and the potential for infection with the relatively large orbital implant. Maximized soft tissue ingrowth into the depths of an implant decreases the inflammatory cell response and potential for infection. (Rubin, P. A. D., et al. "Comparison of Fibrovascular Ingrowth Into Hydroxyapatite and Porous Polyethylene Orbital Implants" Ophthalmic Plastic and Reconstructive Surgery 10(2):96-103 (1994)).
Plaster of Paris is a biocompatible material which is composed of the hemihydrate form of calcium sulfate produced by heating gypsum calcium sulfate dihydrate to drive off water. (Alexander, H., et al., "Calcium-based Ceramics and Composites in Bone Reconstruction" CRC Critical Reviews in Biocompatibility (1987) 4:43-77) It is highly biocompatible and has been successfully used to fill defects in bone (Peltier, L. F., "The Use of Plaster of Paris to Fill Defects in Bone" Clin Orthop (1961) 21:1-31), in dental surgery, and for orbital augmentation (Geist, C. E., et al., "Orbital Augmentation by Hydroxylapatite-based Composites. A Rabbit Study and Comparative Analysis" Ophthalmic Plast Reconstr Surg (1991) 7:8-22). When mixed with HA particles for orbital augmentation, calcium sulfate has been shown to resorb within several weeks of implantation. Moreover, connective tissue ingrowth has been noted in mixtures of HA and calcium sulfate, with minimal inflammation (Geist, C. E., et al., "Orbital Augmentation by Hydroxylapatite-based Composites. A Rabbit Study and Comparative Analysis" Ophthalmic Plast Reconstr Surg (1991) 7:8-22).
Thus, there is need for an orbital implant with as many of the following characteristics as possible: It should be biocompatible, readily vascularized, and have little or no tendency toward extrusion, migration, or infection (see, e.g., Dutton, J. J., "Coralline Hydroxyapatite as an Ocular Implant" Ophthalmology (1991) 98:370-7); it should also serve to impart motility to an artificial eye while supporting the weight of the eye to preserve the delicate, and cosmetically important, structures of the lid; and preferably is capable of being attached to an artificial eye.